Intradermal administration of immunoglobulin g preparation

ABSTRACT

A method for administration of an IgG preparation by an intradermal (ID) route to a subject includes loading with a volume of the IgG preparation an ID delivery device including needles, applying the device to a skin delivery site, using the device to allow dermal penetration of the needles, delivering the volume of the IgG preparation at the skin delivery site, and removing the injection delivery device. The method can be used in the treatment of a disease, such as an immunodeficiency.

BACKGROUND

Field

The present disclosure is related to a method for administration of IgGpreparations by the intradermal (ID) route to a patient in need thereofand a composition for administration of IgG preparations by the ID routeto a patient.

Description of the Related Art

Immunoglobulin G (IgG) is the most abundant immunoglobulin isotype inhuman serum, comprising approximately 80% of all immunoglobulins. IgGpreparations are indicated for the treatment of various diseases such asprimary immunodeficiency, in particular congenital agammaglobulinaemiaand hypogammaglobulinaemia, idiopathic thrombocytopenic purpura, as anadjuvant in the treatment of Kawasaki's Disease and in transplant ofbone marrow, hypogammaglobulinaemia associated with chronic lymphocyteleukaemia as part of HIV infection treatment in pediatric patients,among others.

SUMMARY

In some embodiments, a method for administration of an IgG preparationby an intradermal (ID) route to a subject in need thereof is provided,the method comprising loading with a volume of the IgG preparation an IDdelivery device comprising needles, applying the device to a skindelivery site, using the device to allow dermal penetration of theneedles, delivering the volume of the IgG preparation at the skindelivery site, and removing the delivery device.

In some embodiments of the method, the IgG preparation has an IgGconcentration of about 15% to about 30% (w/v). In some embodiments ofthe method, the IgG preparation has an IgG concentration of about 30%(w/v) or higher.

In some embodiments of the method, a pH of the IgG preparation is about4.5 to about 8.0. In some embodiments of the method, the pH of the IgGpreparation is about 6.5.

In some embodiments of the method, the volume of the IgG preparation isup to about 10 mL per skin delivery site. In some embodiments of themethod, the volume of the IgG preparation is between about 2 mL andabout 8 mL per skin delivery site. In some embodiments of the method,the volume of the IgG preparation is between about 4 mL and about 6 mLper skin delivery site.

In some embodiments of the method, the IgG preparation comprises one ormore additional plasma proteins.

In some embodiments of the method, the subject is a pediatric patient.In some embodiments of the method, the subject is a non-pediatricpatient.

In some embodiments, a composition comprising an IgG preparation fortreatment of a disease in a subject in need thereof is provided.

In some embodiments of the composition, a concentration of IgG in theIgG preparation is about 15% to about 30% (w/v). In some embodiments ofthe composition, the concentration of IgG in the IgG preparation isabout 30% (w/v) or higher.

In some embodiments, the composition has a pH of about 4.5 and about8.0. In some embodiments of the composition, the pH is about 6.5.

In some embodiments of the composition, the subject is a pediatricpatient. In some embodiments of the composition, the subject is anon-pediatric patient.

In some embodiments of the composition, the disease is animmunodeficiency. In some embodiments of the composition, theimmunodeficiency is one of a primary immunodeficiency, a secondaryimmunodeficiency or an acquired immunodeficiency.

In some embodiments of the composition, the IgG preparation comprises anentire IgG molecule, a therapeutically effective fragment of IgG or acombination thereof.

In some embodiments of the composition, the IgG preparation comprisesone or more additional plasma proteins.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure is described below in reference to the followingfigures.

FIG. 1 shows a line graph of plasma human IgG pharmacokinetics at 0-24 hin young farm pigs that were administered an IgG preparation (20 mg/kg)by the IV (n=4), SC (n=4) and ID (n=3) routes.

FIG. 2 shows a line graph of plasma human IgG pharmacokinetics at 0-240h in young farm pigs that were administered an IgG preparation (20mg/kg) by the IV (n=4), SC (n=4) and ID (n=3) routes

DETAILED DESCRIPTION

At present there is high demand for immunoglobulin G (IgG) which ispolyvalent with a wide spectrum of human antibodies and has totalfunctionality (neutralizing capacity, opsonization, half-lifeconserved), with intact molecules (integrity of the crystallizable Fcfragment) and a normal distribution of IgG subclasses identical orequivalent to natural plasma.

The usual routes for the therapeutic administration of IgG preparationsinclude intravenous (IV), subcutaneous (SC) and intramuscular (IM). Inaddition, IgG may be administered by other routes such as the oral,nasal (inhaled) or topical routes. IV administration has become thestandard approach for IgG supplementation in many countries, includingthe United States.

However, although IV administration offers the most useful therapeuticindications, for example, for the treatment of primaryimmunodeficiencies or for variable common immunodeficiency (deficit ofIgG and IgA subclasses), secondary or acquired immunodeficiencies (forexample infection by viruses such as cytomegalovirus, herpes zoster,human immunodeficiency) and diseases of an autoimmune origin(thrombocytopenic purpura, Kawasaki's Syndrome, for example), deliveryof plasma-derived protein therapies such as IgG (Immune globulin G) topatients by IV administration route can be associated withinfusion-related adverse effects such as flushing, fever, chills anddiarrhea. IV infusions also require trained and qualified personnel toadminister.

The current primary alternative to IV administration route for patientsfor IgG is the subcutaneous (SC) route. However, the SC route has beenassociated with slow progression to peak plasma concentration (T_(max)),low plasma area-under-curve (AUC), as well as pain and discomfort.

The intradermal (ID) route, also known as transdermal delivery orpercutaneous permeation, is a non-invasive delivery route which isadvantageous for the administration of many drugs and/or biologics. IDdelivery also overcomes many of the challenges associated withsubcutaneous injection by greatly reducing patient discomfort, needleanxiety, risk of accidental needle stick injury to the personneladministering the injection and issues surrounding sharps disposal. Inaddition, ID systems allow for self-administration, provide sustainedrelease of drugs and/or biologics for periods of time up to one week,and improve patient compliance. Furthermore, ID delivery systems aregenerally inexpensive.

Despite these many advantages, the ID delivery of drugs is confined toclasses of molecules compatible with absorption through the skin.Delivery of therapeutic proteins is not typically viable withtraditional ID delivery, as the skin provides an effective protectivebarrier to these molecules even in the presence of absorption-enhancingexcipients. For example, it has been difficult to exploit the ID routeto deliver macromolecules.

In addition, although much progress has been made in the development ofsystems for ID delivery, most commercially available devices thatprovide ID delivery of liquid formulations remain confined to relativelysmall volumes, typically less than 200 μL. This makes the intradermalsystems not to be considered as a viable alternative for IgG therapy inwhich grams of proteins have to be administered daily.

However, Burton et al. (Burton S. A. et al., Pharmaceutical Research,Vol. 28, Issue 1, pp. 31-40, (2011)) disclosed intradermal delivery intoswine of up to 1.5 mL of a variety of formulations including apolyclonal antibody at a concentration of 57 mg/mL during 5-20 minutesusing a microneedle delivery device. The amount of polyclonal antibodydelivered with this system (approximately 85 mg) is still very low to beconsidered as an option for IgG therapy in which, for example, a patientwith myositis is typically prescribed with 0.4 to 40 gm/kg over fivedays, which can be repeated every 4-6 weeks.

The present disclosure provides a method for ID administration of plasmaproteins in general and IgG in particular. The method of the presentdisclosure overcomes the above-mentioned problems and limitations.

Method

The ID route can provide a novel method for allowing self-administrationof IgG. Thus, in some embodiments, the present disclosure provides amethod for administration of IgG preparations by the ID route. In someembodiments, the method provides for self-administration of IgGpreparations by the ID route. In some embodiments, the method provides asuperior plasma pharmacokinetic profile of IgG as compared to the SCroute. In some embodiments, the method provides a superior plasmapharmacokinetic profile of IgG with a faster T_(max) as compared to theSC route.

In some embodiments, the method provides improved steady state IgGplasma levels due to more frequent dosing regimen, such as a convenientdaily injection of IgG. In some embodiments, the method minimizesinfusion-related adverse events, such as pain and discomfort related toinfusion. In some embodiments, the method improves patient ease ofadministration and compliance.

In some embodiments, the method for administration of an IgG preparationby intradermal route comprises:

-   -   a) loading with a volume of the IgG preparation an ID delivery        device comprising needles;    -   b) applying the device to a skin delivery site;    -   c) using the device to allow dermal penetration of the needles;    -   d) delivering the volume of the IgG preparation at the skin        delivery site; and    -   e) removing the delivery device.

In some embodiments, an ID delivery device comprising needles suitablefor the method of administration of the present disclosure is provided.

In some embodiments, the skin delivery site is proximal to wheretreatment is desired. In some embodiments, the skin delivery site isdistal to where treatment is desired. In some embodiments, the skindelivery site is where it is convenient to administer a drug. In someembodiments, the skin delivery site is where it is convenient toadminister a drug and proximal to where treatment is desired. In someembodiments, the skin delivery site is where it is convenient toadminister a drug and distal to where treatment is desired. In someembodiments, the skin delivery site is convenient forself-administration. In some embodiments, the skin delivery site isconvenient for drug administration for the person administering a drug.

In some embodiments, the method allows for the administration of avolume of up to about 10 mL per site. In some embodiments, the volume isbetween about 2 mL and about 8 mL per site. In some embodiments, thevolume is between about 4 mL and about 6 mL per site. In someembodiments, the volume is about 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14 or 15 mL per site.

In some embodiments, the volume is dependent on the injection solutioncharacteristics. In some embodiments, the volume is dependent on theviscosity of the IgG preparation. In some embodiments, the volume isdependent on the IgG concentration in the IgG preparation. In someembodiments, the volume is dependent on the limitation of the selectedID injection device.

The duration of therapy by the method can vary, without limitation, onthe nature of a disease, age of a subject, frequency of administration,dose of IgG preparation, patient compliance, quality and effectivenessof the IgG preparation.

In some embodiments, the duration and frequency of administration dependon, without limitation, the amount of IgG administered, how rapidly theIgG preparation is administered and the pharmacokinetics andpharmacodynamics of the IgG preparation. For example, in someembodiments, the duration of treatment can range from about 1 day toabout 28 days. In some embodiments, the duration of treatment can be forabout 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 21, 22, 23, 24, 25, 26, 27 or 28 days. In some embodiments, theduration of treatment can be for about 1 week to about 52 weeks. In someembodiments, the duration of treatment can be for about 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27,28, 29 or 30 weeks. In some embodiments, the duration of treatment isindefinite, for example, the lifetime of a patient. In some embodiments,the frequency of administration is daily. In some embodiments, thefrequency of administration is once, twice, thrice or four times daily.In some embodiments, the frequency of administration is daily and theduration of treatment is indefinite. In some embodiments, the frequencyof administration is once, twice, thrice or four times daily and theduration of treatment is indefinite.

In some embodiments of the present method, a daily administrationregimen would result in more stable plasma concentrations of IgG ascompared to IV infusion or SC administration every 3-4 weeks.

In some embodiments, the method comprises using the IgG preparation forthe treatment of a disease. In some embodiments, the disease comprisesprimary immunodeficiency. In some embodiments, the primaryimmunodeficiency comprises congenital agammaglobulinaemia andhypogammaglobulinaemia and idiopathic thrombocytopenic purpura. In someembodiments, the primary immunodeficiency is a pediatric primaryimmunodeficiency. In some embodiments, the pediatric primaryimmunodeficiency is hypogammaglobulinaemia associated with chroniclymphocyte leukaemia. In some embodiments, the pediatric primaryimmunodeficiency is hypogammaglobulinaemia associated with chroniclymphocyte leukaemia as part of HIV infection treatment in pediatricpatients.

In some embodiments, the immunodeficiency is a variable commonimmunodeficiency. In some embodiments, the variable commonimmunodeficiency is deficiency of the IgG subclass. In some embodiments,the immunodeficiency is a secondary or acquired immunodeficiency. Insome embodiments, the secondary or acquired immunodeficiency is due toinfection, for example, by viruses such as cytomegalovirus, herpeszoster virus, human immunodeficiency virus. In some embodiments, thesecondary or acquired immunodeficiency is due to a disease of autoimmuneorigin, for example, thrombocytopenic purpura, Kawasaki's Syndrome. Insome embodiments, the IgG preparation can be used as an adjuvant in thetreatment of Kawasaki's disease and in bone marrow transplant.

In some embodiments, the method comprises treatment of immunodeficiencyin a patient. In some embodiments, the immunodeficiency is primaryimmunodeficiency. In some embodiments, the immunodeficiency is primaryimmunodeficiency in a pediatric patient. In some embodiments of themethod for treating primary immunodeficiency, the concentration of IgGis about 15% to about 30% (w/v). In some embodiments of the method fortreating primary immunodeficiency, the concentration of IgG is about 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30% (w/v). Insome embodiments of the method for treating primary immunodeficiency,the concentration of IgG is about 30% (w/v) or higher. In someembodiments of the method, the IgG preparation has a pH of about 4.5 toabout 8.0. In some embodiments of the method, the IgG preparation has apH of about 6.5. In some embodiments of the method, the IgG preparationhas a pH of about 4.5, 4.75, 5.0, 5.25, 5.5, 5.75, 6.0, 6.25, 6.5, 6.75,7.0, 7.25, 7.5, 7.75 or 8.0.

In some embodiments, the age of the subject is from about 10, 15 or 18years to about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 or 70 years. Insome embodiments, the age of the subject is lower than about 10 years.In some embodiments, the age of the subject is higher than about 70years. In some embodiments, the method enables treatment of pediatricpatients. In some embodiments, the age of the pediatric patient canrange from about 1 day to about 18 years. In some embodiments, the sexof the subject is a male. In some embodiments, the sex of the subject isa female.

In some embodiments, the method can be practiced in a hospital, anursing home, an old age home or a pediatric care facility. In someembodiments, the method can be practiced at home. In some embodiments,the method comprises self-administration, administration by a healthcare worker or administration by a family member.

In some embodiments, the present disclosure provides a method for thedelivery of a therapeutic plasma protein to a patient in need thereof.In some embodiments, the therapeutic plasma protein is an entire IgG. Insome embodiments, the therapeutic plasma protein is a therapeuticfragment of an IgG. In some embodiments, the present disclosure providesa method for self-administration of a therapeutic plasma protein. Forexample, in some embodiments, a patient with a primary immunodeficiencycould self-administer a therapeutic plasma protein such as IgG at homerather than going to a clinic for IV administration of the therapeuticplasma protein. The present method provides an administration route thatis convenient and less painful as compared to other routes ofadministration and therefore could lead to greater patient compliance.

Composition

In some embodiments, the composition is an IgG preparation. In someembodiments, the composition is an IgG solution. In some embodiments,the concentration of IgG can be between about 15% and about 30% (w/v).In some embodiments, the concentration is about 7% to about 14%. In someembodiments, the concentration is about 23% to about 30%. In someembodiments, the concentration is about 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30%(w/v). In some embodiments, the concentration is about 30% or higher.

In some embodiments, the composition comprises the entire IgG molecule.In some embodiments, the composition comprises IgG fragments that aretherapeutically effective. In some embodiments, the composition cancomprise additional antibody types such as IgM, IgA or a combinationthereof.

In some embodiments, the composition comprises IgG for the treatment ofimmunodeficiency in a patient in need thereof. In some embodiments, thecomposition for treating immunodeficiency has an IgG concentration ofabout 15% to about 30% (w/v). In some embodiments, the composition fortreating immunodeficiency has an IgG concentration of about 30% (w/v) orhigher. In some embodiments, the composition for treatingimmunodeficiency has a pH of about 4.5 to about 8.0. In someembodiments, the composition for treating immunodeficiency has a pH ofabout 6.5. In some embodiments, the immunodeficiency is primaryimmunodeficiency. In some embodiments, the immunodeficiency is primaryimmunodeficiency in a pediatric patient.

In some embodiments, the pH of the IgG solution can be between about 4.5and about 8.0. In some embodiments, the pH is about 4.5, 4.75, 5.0,5.25, 5.5, 5.75, 6.0, 6.25, 6.5, 6.75, 7.0, 7.25 7.5, 7.75 or 8.0. Insome embodiments, the pH is about 6.5. The pH of the IgG preparationdoes not cause scabbing of the skin at administration site and is welltolerated.

In some embodiments, the composition is delivered at a skin deliverysite that is proximal to where treatment is desired. In someembodiments, the composition is delivered at a skin delivery site thatis distal to where treatment is desired. In some embodiments, the skindelivery site is where it is convenient to administer a drug. In someembodiments, the skin delivery site is where it is convenient toadminister a drug and proximal to where treatment is desired. In someembodiments, the skin delivery site is where it is convenient toadminister a drug and distal to where treatment is desired. In someembodiments, the skin delivery site is convenient forself-administration. In some embodiments, the skin delivery site isconvenient for drug administration for the person administering a drug.

In some embodiments, the composition is administered at a volume of upto about 10 mL per site. In some embodiments, the volume is betweenabout 2 mL and about 8 mL per site. In some embodiments, the volume isbetween about 4 mL and about 6 mL per site. In some embodiments, thevolume is about 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14 or 15 mL per site.

In some embodiments, the volume is dependent on the injection solutioncharacteristics. In some embodiments, the volume is dependent on theviscosity of the IgG preparation. In some embodiments, the volume isdependent on the IgG concentration in the IgG preparation. In someembodiments, the volume is dependent on the limitation of the selectedID injection device.

In some embodiments, the duration and frequency of administration of thecomposition depend on, without limitation, the amount of IgGadministered, how rapidly the IgG preparation is administered and thepharmacokinetics and pharmacodynamics of the IgG preparation. Forexample, in some embodiments, the duration of treatment can range fromabout 1 day to about 28 days. In some embodiments, the duration oftreatment can be for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or 28 days. Insome embodiments, the duration of treatment can be for about 1 week toabout 52 weeks. In some embodiments, the duration of treatment can befor about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29 or 30 weeks. In some embodiments, theduration of treatment is indefinite, for example, the lifetime of apatient. In some embodiments, the frequency of administration is daily.In some embodiments, the frequency of administration is once, twice,thrice or four times daily. In some embodiments, the frequency ofadministration is daily and the duration of treatment is indefinite. Insome embodiments, the frequency of administration is once, twice, thriceor four times daily and the duration of treatment is indefinite.

In some embodiments, the composition comprises an IgG preparation forthe treatment of a disease. In some embodiments, the disease comprisesprimary immunodeficiency. In some embodiments, the primaryimmunodeficiency comprises congenital agammaglobulinaemia andhypogammaglobulinaemia and idiopathic thrombocytopenic purpura. In someembodiments, the primary immunodeficiency is a pediatric primaryimmunodeficiency. In some embodiments, the pediatric primaryimmunodeficiency is hypogammaglobulinaemia associated with chroniclymphocyte leukaemia. In some embodiments, the pediatric primaryimmunodeficiency is hypogammaglobulinaemia associated with chroniclymphocyte leukaemia as part of HIV infection treatment in pediatricpatients.

In some embodiments, the immunodeficiency is a variable commonimmunodeficiency. In some embodiments, the variable commonimmunodeficiency is deficiency of the IgG subclass. In some embodiments,the immunodeficiency is a secondary or acquired immunodeficiency. Insome embodiments, the secondary or acquired immunodeficiency is due toinfection, for example, by viruses such as cytomegalovirus, herpeszoster virus, human immunodeficiency virus. In some embodiments, thesecondary or acquired immunodeficiency is due to a disease of autoimmuneorigin, for example, thrombocytopenic purpura, Kawasaki's Syndrome. Insome embodiments, the IgG preparation can be used as an adjuvant in thetreatment of Kawasaki's disease and in bone marrow transplant.

In some embodiments, the composition comprises treatment ofimmunodeficiency in a patient. In some embodiments, the immunodeficiencyis primary immunodeficiency. In some embodiments, the immunodeficiencyis primary immunodeficiency in a pediatric patient. In some embodiments,the composition is for treating primary immunodeficiency, theconcentration of IgG is about 15% to about 22% (w/v). In someembodiments, the composition is for treating primary immunodeficiency,the concentration of IgG is about 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29 or 30% (w/v). In some embodiments of thecomposition for treating primary immunodeficiency, the concentration ofIgG is about 30% (w/v) or higher. In some embodiments of thecomposition, the IgG preparation has a pH of about 4.5 to about 8.0. Insome embodiments of the composition, the IgG preparation has a pH ofabout 6.5. In some embodiments of the composition, the IgG preparationhas a pH of about 4.5, 4.75, 5.0, 5.25, 5.5, 5.75, 6.0, 6.25, 6.5, 6.75,7.0, 7.25, 7.5, 7.75 or 8.0.

In some embodiments, the age of the subject is from about 18 years toabout 70 years. The age of the subject may be 10, 15, 20, 25, 30, 35,40, 45, 50, 55, 60, 65 or 70 years. In some embodiments, the age of thesubject is lower than about 18 years. In some embodiments, the age ofthe subject is higher than about 70 years. In some embodiments, thecomposition enables treatment of pediatric patients. In someembodiments, the age of the pediatric patient can range from about 1 dayto about 18 years. In some embodiments, the sex of the subject is amale. In some embodiments, the sex of the subject is a female.

In some embodiments, the composition can be administered in a hospital,a nursing home, an old age home or a pediatric care facility. In someembodiments, the composition can be administered at home. In someembodiments, the composition can be self-administered, administered by ahealth care worker or administered by a family member.

EXAMPLES Example 1 Administration of an IgG Preparation to Pigs Via IV,SC and ID

Young farm pigs (20-25 kg) were administered with IgG (20 mg/kg) by theIV (n=4), SC (n=4) and ID (n=3) routes. Venous blood samples wereobtained at 2, 30 and 60 min; 3 and 6 hours and then daily for 10 daysafter IgG administration for measurement of human-specific IgG byimmunoassay.

As shown in FIG. 1, the ID route had faster uptake of IgG into theplasma compartment as compared to the SC route. The plasma concentrationof IgG approached C_(max) within 1 hour after administration by the IDroute, whereas C_(max) for the SC route was not achieved for 24 hours.FIG. 1 and FIG. 2 show the time course of plasma IgG afteradministration by IV, ID and SC routes. The same plasma pharmacokineticdata are shown 0-24 hours (FIG. 1) as well as on a compressed X-axisover 10 days (FIG. 2). Clearly, 24 hours onwards in this experimentalmodel, the plasma levels of IgG are similar irrespective of the route ofadministration. Thus, the elimination half-life (T^(1/2)) for all threeroutes is very similar.

Example 2 Influence of IgG Preparation pH on the Delivery Site

To evaluate the influence of the IgG preparation pH on the deliverysite, 2 mL of Gamunex® and IGSC 20% IgG formulations (GrifolsTherapeuctics Inc., USA) both at pH 4.0, and IGIM-S/D (GrifolsTherapeuctics Inc., USA) at pH 6.5, were administered to young farmpigs.

Three days following 2 mL administration of IgG, the low pHadministration causes scabbing of the skin at administration sitewhereas neutral pH IgG appears to have good tolerability.

Example 3 Pediatric Treatment

The method according to the present disclosure can be used for treatinga pediatric patient with a primary immunodeficiency. The weight of thepatient is about 25 kg. The typical dose range for such a patient isabout 300 to about 800 mg/kg body weight over about 4 weeks. This doescan be achieved using the present method with one ID administration ofabout 2 mL or about 4 mL of a concentrated IgG preparation. Theconcentrated IgG preparation has a concentration of IgG of about 16.5%or about 20% (w/v).

What is claimed is:
 1. A method for administration of an IgG preparationby an intradermal (ID) route to a subject in need thereof, the methodcomprising: a) loading with a volume of the IgG preparation an IDdelivery device comprising needles; b) applying the device to a skindelivery site; c) using the device to allow dermal penetration of theneedles; d) delivering the volume of the IgG preparation at the skindelivery site; and e) removing the delivery device.
 2. The methodaccording to claim 1, wherein the IgG preparation has an IgGconcentration of about 15% to about 30% (w/v).
 3. The method accordingto claim 1, wherein the IgG preparation has an IgG concentration ofabout 30% (w/v) or higher.
 4. The method according to claim 1, wherein apH of the IgG preparation is about 4.5 to about 8.0.
 5. The methodaccording to claim 4, wherein the pH of the IgG preparation is about6.5.
 6. The method according to claim 1, wherein the volume of the IgGpreparation is up to about 10 mL per skin delivery site.
 7. The methodaccording to claim 6, wherein the volume of the IgG preparation isbetween about 2 mL and about 8 mL per skin delivery site.
 8. The methodaccording to claim 6, wherein the volume of the IgG preparation isbetween about 4 mL and about 6 mL per skin delivery site.
 9. The methodaccording to claim 1, wherein the IgG preparation comprises one or moreadditional plasma proteins.
 10. The method according to claim 1, whereinthe subject is a pediatric patient.
 11. The method according to claim 1,wherein the subject is a non-pediatric patient.
 12. The method accordingto claim 1, wherein the subject is in need of treatment for a disease.13. The method according to claim 12, wherein the disease is animmunodeficiency.
 14. The method according to claim 13, wherein theimmunodeficiency is one of a primary immunodeficiency, a secondaryimmunodeficiency or an acquired immunodeficiency.
 15. The methodaccording to claim 1, wherein the IgG preparation comprises an entireIgG molecule, a therapeutically effective fragment of IgG or acombination thereof.